Real-World Demographics, Clinical Characteristics, and Predictors of Persistence Among Males with Rett Syndrome Treated with Trofinetide

INTRODUCTION: Rett syndrome (RTT) is a rare neurodevelopmental disease that primarily affects females but also occurs in males. Trofinetide (TROF) is approved in the USA and Canada for individuals with RTT regardless of sex aged ≥ 2 years; efficacy and safety of TROF was primarily studied among females, thus real-world data for males remain limited. This study evaluated real-world characteristics, treatment persistence, and predictors of non-persistence among males with RTT. METHODS: This retrospective cohort study using IQVIA database linked to TROF specialty pharmacy claims from 01/01/2021 to 09/30/2024 identified males with ≥ 1 medical claim for RTT (ICD-10 F84.2). Two groups were created based on treatment status and their respective index dates: treated and untreated. Continuous enrollment of ≥ 6 months pre-index and post-index was required. Pre-index demographics and clinical characteristics were compared descriptively. Among treated males, Kaplan-Meier analysis assessed time to non-persistence, and logistic regression evaluated predictors of non-persistence. RESULTS: Of 8047 individuals with RTT identified in the database, 1219 (15.1%) were males; of these, 75 (6.2%) were treated with TROF and 1144 (93.8%) were untreated; after final study criteria, 51 (10.9%) were treated and 415 (89.1%) were untreated. The mean (SD) age for treated vs untreated males was 18.8 (18.3) vs 17.7 (13.2) years. Neurologists managed most patients treated with TROF (64.7% vs 12.7%). Treated males had higher pre-index rates of epilepsy (52.9% vs 25.5%), gastrostomy (31.4% vs 16.1%), and respiratory failure (25.5% vs 13.3%) than untreated (all p < 0.05). Among treated males, 52.9% were persistent and 47.1% were non-persistent. Approximately 70% remained on TROF for ≥ 6 months and > 50% for ≥ 17 months. Pre-index neurologic disorders were significantly associated with non-persistence. CONCLUSIONS: Most males with RTT remained untreated during this study period, while TROF initiation appeared concentrated among those with greater pre-index concomitant comorbidities and neurology involvement. Persistence beyond 6 months was common, supporting continued long-term use of TROF in males with RTT in real-world practice.